A diet high in vitamin A or its analogues may help adolescents and young adults with acute lymphoblastic leukaemia (ALL) reduce their risk of painful pancreatic inflammation during chemotherapy, according to a study.
Details about this potential dietary solution to prevent a potentially fatal adverse event were published in Science Translational Medicine on March 15, 2023.
Sohail Husain, MD, chief of Pediatric Gastroenterology, Hepatology, and Nutrition at Stanford University, and Anil Goud Jegga, DVM, MRes, a computational biologist at Cincinnati Children’s Hospital Medical Center, led the research team. Treatment with the enzyme asparaginase helps starve cancer cells by lowering the amount of asparagine circulating in the blood, which cancer cells require but cannot produce.
The medication, which is frequently used in conjunction with other chemotherapies, is administered by injection into a vein, muscle, or under the skin. However, an estimated 2% to 10% of asparaginase users develop pancreatic inflammation as a result of asparaginase treatment. The symptoms can be severe for one-third of these people.
Jegga and colleagues used over 100 million data points from gene expression data, small-molecule data, and electronic health records to better understand the mechanisms underlying asparaginase-associated pancreatitis (AAP) and to identify potential interventions to prevent or mitigate AAP.
First, they analysed massive amounts of gene expression data to discover that retinoids could reverse gene activity associated with asparaginase or pancreatitis (vitamin A and its analogs). More evidence was discovered by “mining” millions of electronic health records from the TriNetX database and the US Food and Drug Administration Adverse Event Reporting System.
The AERSMine software developed at Cincinnati Children’s by Mayur Sarangdhar, PhD, MRes, and colleagues was used in this number crunching and predictive analytics work. The researchers also analysed data from mouse experiments and compared plasma samples from ALL patients who developed pancreatitis to those who did not.
Finally, the team came up with two sets of human “real-world” experiences. They discovered that when asparaginase was combined with vitamin A, only 1.4% of patients developed pancreatitis, compared to 3.4% of patients who did not. Concurrent vitamin A use was associated with a 60% reduction in the risk of AAP. Lower dietary vitamin A levels were linked to an increased risk and severity of AAP.
“This study demonstrates the potential of mining ‘real-world’ data to identify therapy modifiers for improving patient outcomes. In cases where a primary drug induces toxicity but is critical to therapy, such as asparaginase, therapy modifiers, such as vitamin A and its analogs, may be of immediate relevance to patients on asparaginase and ‘at-risk’ for AAP,” says Sarangdhar, a co-first author of the study.
Says Jegga: “Our study highlights the power of heterogeneous data integration and analysis in translational research. By leveraging existing ‘omics and patient-centric data and a systems approach, we were able to identify new insights into the development of AAP and potential interventions to prevent or mitigate this side effect.”
Next steps
In some ways, the findings of this study could be immediately applied to patient care. More clinical research is needed, however, to determine how much vitamin A is required to protect ALL patients from pancreatitis, and whether a protective level can be achieved through diet or supplements. In fact, target vitamin levels may need to vary based on individual metabolic differences.
